A program project is proposed by researchers at the John Hopkins Medical Institutions and the University of California at Berkeley entitled "High Throughput Genetic analysis of Primary Bladder Cancer and Urine Sediment"> The goals of this proposal are to improve our understanding of the molecular genetic changes that drive bladder cancer progression as we develop and integrate novel high throughput approaches for the detection of these genetic alterations. These approaches will be used to translated our findings into the clinical setting where we will evaluate genetic alterations as predictors of disease outcome and targets for molecular detection. We intend to accomplish these goals by addressing the following specific aims in project #1; 1) to identify and characterize key genetic alterations in primary bladder cancer 2) to place these genetic changes in a molecular progression model 3) to identify microsatellite loci susceptible to instability and 4) to integrate the aforementioned genetic targets into molecular detection strategies. In project #2, we will develop high throughput platforms by 1) building a monster-capillary array electrophoresis (MCAE) scanner at Berkeley 2) transferring this technology to Hopkins initially at 256 lane capacity and then to 3) 1024 lane capacity 4) Synthesis and evaluation of Energy transfer (ET) primers and 5) building and transferring CAE on glass (chip) substrates. In project #3, we will use established genetic changes form projects #1 and 2 to 1) test these alterations as predictors of prognosis and disease outcome 2) validate early detection strategies based on microsattelite analysis in urine and 3) test new molecular approaches in serum as markers of disease burden. Unlike traditional methods of isolated investigators, this program emphasizes sharing of subjects, tissue samples, resources, technical expertise and data analysis strategies. Our program will not only offer clinical direction for basic research efforts, but will also facilitate the direct translation of state-of-the-art high throughput technology into the basic laboratory and clinical area.